Effects Of NRG1Gene Polymorphisms And Clinical Features On Cognitive Functions In Childhood And Adolescence-onset Schizophrenia

Objectives1. To explore the differences of NRG1gene polymorphisms (rs10503929、 rs3924999、rs6994992) among childhood and adolescence-onset schizophrenia patients and normal controls;2. To study the association between NRG1gene polymorphisms and cognition functions in childhood and adolescence-onset schizophrenia;3. To discuss the effects of different clinical features on cognitive functions in childhood and adolescence-onset schizophrenia patients.Methods78childhood and adolescence-onset schizophrenia (hereinafter briefly referred to as children group) and74adult-onset schizophrenia (hereinafter briefly referred to as adult group) ICD-10(international classification of diseases-10, ICD-10) criteria defined schizophrenia of Chinese Han and129normal controls were enrolled in the study and extracted venous blood. Rs10503929, rs3924999and rs6994992of NRG1gene were genotyped. Cognitive function test scores and clinical features which potentially influence cognition functions were collected. C-WISC(Chinese Wechsler Intelligence Scale for Children)、CPT (Continuous Performance Test), WCST (Wisconsin Card Sorting Test) and P300and so on were collected as cognitive function indicators. Both genetic and non-genetic factors, including sex, ages, education years and so on were also collected as potential indicators which may affect cognition functions.Results1. In the polymorphisms loci of NRG1gene rs3924999, statistically significant differences of three kinds of genotype frequencies and two kinds of allele frequencies were found between adult group and control group (all p＜0.05). G/G and G/A genotype frequencies of adult group were inferior to the controls, whereas A/A genotype frequencies were superior to the controls. Correspondingly, G allele frequencies in adult group are inferior to the controls and A allele frequencies are superior to the controls.2. Significant differences of P300latency among three genotypes of rs3924999were found at Fz in the children group, and the G/G carriers of rs3924999tended to perform better in the P300N2latency as compared to A/A or G/A carriers (p＜0.05);Significant differences of VIQ and PIQ among three genotypes of rs6994992were also found in the children group, and the T/T carriers of rs6994992tended to perform better as compared to C/T carriers (p＜0.05).3. Binary logistic regression in children group revealed that:patients with lower education level or earlier onset of age had longer P3latency of P300at Fz area; patients with higher parental education level had higher scores of FIQ, VIQ, PIQ, conceptual level and completed categories of WCST and backward numeric order reciting:patients with higher PANSS negative、depression or total scores had lower scores of FIQ、VIQ、PIQ、completed categories and conceptual level of WCST and backward numeric order reciting; patients with longer stabilization time had higher backward numeric order reciting scores.Conclusions1.Rs3924999of NRG1gene is a schizophrenia susceptibility loci;2.Both genetic and non-genetic factors affect the cognitive functions of childhood and adolescence-onset schizophrenia patients, and the patients with higher own and parental education level, longer stabilization time, later onset of age. lower PANSS total scores, negative scores and the depression scores,and carrying with rs3924999G/G genotype and rs6994992T/T genotype showed better cognitive functions.